The mechanisms by which hormones and growth factors stimulate the somatic growth of the fetus are poorly understood. Most of the hormones known to stimulate post-natal growth have been shown to exert little or no effect on fetal growth. The overall goal of this project is to delineate the primary hormonal stimulators of fetal somatic growth. Particular emphasis is placed on efforts to test the hypothesis that the somatomedin family of peptides are important in the growth of the human fetus. This objective will be pursued by carrying out studies designed to: 1) Assess the role of somatomedin and other growth factors in the stimulation of growth in vitro of cultured fetal cells. This will be achieved by study of the stimulatory effects of serum components, extracellular matrices, conditioned media from fetal cells and tissues, and purified human somatomedin-C. 2) Determine the site of origin and the chemical nature of somatomedin synthesized by the fetus. Specifically, we will attempt to determine how early in embryonic life somatomedin-C is produced and whether it is produced by all embryonic cell types. We also will perform studies to characterize the somatomedin produced when isolated mRNA is translated in vitro. 3) Assess the physiological control of somatomedin-C in serum from fetuses and newborns and during gestation in mothers. This will be accomplished by determining the relationship of cord serum somatomedin-C with fetal size in healthy infants and infants with abnormalities of fetal growth. We also will do studies in fetuses and young experimental animals to determine whether growth hormone and growth hormone-like peptides are important in maintenance of somatomedin.